Induction Chemoimmunotherapy Combined With Chemoradiotherapy in Esophageal Cancer

Efficacy and Safety of Inductive Chemoimmunotherapy Followed by Chemoradiotherapy With or Without Surgery in Locally Advanced Esophageal Squamous Cell Cancer: a Single-arm, Prospective, Phase II Trial

Although unprecedented advances have been made in the field of esophageal cancer in recent decades, the prognosis for patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains extremely poor, accounting for 30-40% of overall survival at 5 year. In recent years, multimodal treatments have proven to be an appropriate therapeutic approach for locally advanced ESCC. Recently, immunotherapy developed rapidly. The purpose of this study was to observe the efficacy and safety of cardonilizumab combined with chemoradiotherapy in the treatment of locally advanced ESCC.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer; Surgery; Immunotherapy; Chemoradiotherapy; Induction Therapy
• Intervention / Treatment: Drug: Cardonilizumab; Radiation: Chemoradiotherapy ±immunotherapy; Procedure: Radical surgery

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xin Wang, M.D.; Phone Number: +861013311583220; Email: beryl_wx2000@163.com

Study Locations

• China
  • Beijing, China, 100021
    • Recruiting
    • Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
    • Contact: Xin Wang, MD; Phone Number: +861013311583220; Email: beryl_wx2000@163.com
  • Henan
    • Anyang, Henan, China
      • Not yet recruiting
      • Anyang Cancer Hospital
      • Contact: Xiaomin Wang, M.D.
    • Xinxiang, Henan, China
      • Not yet recruiting
      • The First Affiliated Hospital of Xinxiang Medical University
      • Contact: Xiaomei Liu, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-80 years old；
• Eligible patients were histologically confirmed esophageal squamous cell carcinoma;
• Eligible patients were proven locally advanced ESCC (cT1-2N1-3M0-1, cT3/T4N0-3M0-1, M1 was limited to supraclavicular lymph node metastasis）diagnosed by computed tomography [CT] and/or endoscopic ultrasonography [EUS] according to the American Joint Committee on Cancer (AJCC) 8th edition staging system；
• ECOG PS score: 0~1；
• Main organs and bone marrow function are normal: routine blood tests: hemoglobin (Hb) ≥100g/L ; absolute neutrophil count (NEUT)≥1.5×109/L; platelets (PLT) ≥100×109/L; white blood cell (WBC)≥3.5×109/L,biochemical examination: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5×UNL; serum total bilirubin (TBIL) ≤1.5×UNL; serum creatinine ( Cr) 1.0×1.5UNL, and BUN≤1.0×UNL;

Exclusion Criteria:

• Those combined with other primary malignant tumors other than esophageal cancer (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
• patients who had previously received other treatments
• At the time of diagnosis, there were distant and hematogenous metastases beyond the supraclavicular lymph node region, including retroperitoneal multiple lymph node metastasis, bone metastasis, brain metastasis, lung metastasis, liver metastasis, malignant pleural effusion and ascites
• Those who already have esophageal perforation or are at high risk of esophageal perforation
• Patients whose tumors invade close to large blood vessels and are at risk of bleeding in the
• there are active infections, such as active tuberculosis and hepatitis
• There are contraindications to immunotherapy.
• Pregnant or lactating women and women of childbearing age do not take reliable contraceptive measures
• Combined with serious cardiovascular diseases, such as uncontrolled heart failure, coronary heart disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or a history of myocardial infarction within the past 6 months; and those combined with other uncontrolled acute and chronic diseases such as hypertension and diabetes.
• Violation of inclusion and exclusion criteria, or other reasons that the researcher believes cannot continue the study of drug treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Inductive chemoimmunotherapy+chemoradiotherapy±surgery; In this group, the patients were given 2 cycles of inductive therapy of cardonilizumab combined with chemotherapy, followed by concurrent chemoradiotherapy with two cycles of nab-paclitaxel and cisplatin plus radiotherapy of 50-50.4 Gy. After clinical evaluation, surgery was feasible for a part of patients.

Drug: Cardonilizumab; Two cycles of Inductive therapy： nab-paclitaxel 250mg/ m2+cisplatin 75mg/ m2+Cardonilizumab 10mg/kg，ivgtt，3 weeks per cycle for 2 cycles; Radiation: Chemoradiotherapy ±immunotherapy; Chemoradiotherapy ± immunotherapy： PTV: 50-50.4Gy/1.8-2Gy/25-28fractions ②nab-paclitaxel 100mg+cisplatin 25mg/ m2, d1, every 7 days for 3-5 weeks ③Cardonilizumab 10mg/kg，ivgtt，3 weeks per cycle for 2 cycles; Procedure: Radical surgery; Surgery was evaluated after concurrent chemoradiotherapy according to patients willing and the surgeons' assessment. If patients were accessed with unresectable disease after radiotherapy or refused to receive surgery, Cardonilizumab would be administered for 2 years or until disease progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival	Time from treatment initiation to locoregional or distant recurrence, or death from any cause.	1-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The 1-year OS rate was defined as the proportion of patients who still alive within one year from treatment initiation.	1-year
Adverse events	In terms of adverse events of radiation, chemotherapy and immunotherapy	1-year
Locoregional recurrence free survival	The 1-year rate was defined as the proportion of patients who did not have any locoregional recurrence from treatment initiation.	1-year
Distant metastasis free survival	The 1-year rate was defined as the proportion of patients who did not have any distant metastasis from treatment initiation.	1-year

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Xin Wang, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 10, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Immunomodulating Agents
• Other Study ID Numbers: NCC4475

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No